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Frontiers in Endocrinology 202211-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide...
BACKGROUND AND OBJECTIVES
11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.
DESIGN AND METHODS
We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.
RESULTS
We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.
CONCLUSIONS
11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework, 10.17605/OSF.IO/NR7UV.
Topics: Adrenal Gland Neoplasms; Adrenal Hyperplasia, Congenital; Adult; Aldosterone; Carcinoma; Desoxycorticosterone; Female; Humans; Hyperplasia; Hypertension; Male; Middle Aged
PubMed: 35432204
DOI: 10.3389/fendo.2022.846865 -
Arab Journal of Urology 2021While most men with non-obstructive azoospermia (NOA) are not amenable to medical treatment, some men can be treated effectively with hormonal therapy, prior to... (Review)
Review
While most men with non-obstructive azoospermia (NOA) are not amenable to medical treatment, some men can be treated effectively with hormonal therapy, prior to considering surgery. In some cases, hormonal therapy alone can treat NOA, without the need for surgery. In other cases, correction of a potential hormonal imbalance can enhance the chances of success of surgical sperm retrieval (SSR), with either conventional or microdissection testicular sperm extraction. Abnormal testicular function and low androgen levels can result from a primary dysfunction, a medical or surgical condition, or from an exogenous factor, and should be managed prior to more invasive interventions. Even men with normal androgen levels may benefit from hormonal therapy before sperm retrieval. Moreover, SSR may cause testicular injury and aggravate the pre-existing situation. If surgical extraction of sperm fails, it leaves the patients with less satisfactory options, like donor sperm or adoption. Therefore, it is the role of the infertility specialist to be vigilant and identify reversible causes of NOA, such as hormonal imbalance, prior to considering surgery. In the present paper we will systematically review the literature and highlight the available conventional medical regimens, as well as experimental ones. : ART: assisted reproductive technology; CAH: congenital adrenal hyperplasia; EAU: European Association of Urology; hCG: human chorionic gonadotrophin; HH: hypogonadotrophic hypogonadism; hMG: human menopausal gonadotrophin; IUI: intrauterine insemination; micro-TESE: microdissection testicular sperm extraction; NOA: non-obstructive azoospermia; OR: odds ratio; SCO: Sertoli-cell only; SERM: selective oestrogen receptor modulator; SRR: sperm retrieval rate; SSC: spermatogonia stem cell; TART: testicular adrenal rest tumour; WMD: weighted mean difference.
PubMed: 34552772
DOI: 10.1080/2090598X.2021.1956233 -
Frontiers in Endocrinology 2021Congenital adrenal hyperplasia (CAH) is a group of congenital genetic diseases caused by defective steroidogenesis. Our study aims to systematically analyze the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is a group of congenital genetic diseases caused by defective steroidogenesis. Our study aims to systematically analyze the screening results for CAH in Chinese newborns.
METHODS
Studies were searched from PubMed, Web of Science, Cochrane library and some Chinese databases up to September, 2020. Meta-analysis was performed after quality assessment and data extraction.
RESULTS
After a review of 2 694 articles, we included 41 studies enrolling 7 853 756 newborns. In our study, we found that the incidence of CAH in China was 0.43‱ [95% confidence intervals(CI), (0.39‱, 0.48‱)], or 1/23 024 [95%CI, (1/25 757,1/20 815)]. 27 studies were included for analysis of the screening positive rate, which gave a rate of 0.66% [95%CI, (0.54%, 0.78%)]. As for the recall rate of positive cases, 17 studies were included and showed that the recall rate reached 86.17% [95%CI, (82.70%, 89.64%)]. Among the CAH patients, the ratio of males to females was 1.92:1 (119:62), and the ratio of salt wasting (SW) to simple virilization (SV) type was 3.25:1 (104:32). The average 17-hydroxyprogesterone (17-OHP) value of CAH was 393.40 ± 291.85 nmol/L (Range 33-1 300 nmol/L); there was no significant difference between male and female patients (437.17 ± 297.27 nmol/L v.s. 322.25 ± 293.04 nmol/L, =0.16), but a significant difference was found between SW and SV patients (483.29 ± 330.07 nmol/L v.s. 73.80 ± 7.83nmol/L, =0.04).
CONCLUSION
We systematically analyzed the current situation of neonatal CAH screening in China, which will deepen our understanding for future CAH screening and early diagnosis.
Topics: Adrenal Hyperplasia, Congenital; China; Female; Humans; Infant, Newborn; Male; Neonatal Screening
PubMed: 33967952
DOI: 10.3389/fendo.2021.624507 -
Revista Da Associacao Medica Brasileira... Dec 2020There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome,...
There is no pooled information about pelvic floor parameters (muscle assessment, disorders) of women with gynecologicaL endocrinopathies (eg. polycystic ovary syndrome, congenital adrenal hyperplasia, premature ovarian insufficiency). Given that, a systematic review was performed on the Pubmed, Scopus, Google Scholar, Scielo and PEDro databases regarding the main gynecological endocrinopathies [polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPL)] since their inception to April 2020. Data quality assessment was made by the Newcastle-Ottawa Scale (NOS) adapted for cross-sectional studies. A total of 4,272 results were retrieved from all databases. After excluding duplicate results and screening by title and abstract, nine studies were selected for quantitative analysis. Seven studies were performed with women with PCOS and two studies with POI. Women with PCOS presented a higher prevalence of urinary incontinence (UI) among obese women, a higher thickness of the levator ani muscle, and higher levels of muscle activity measured by surface electromyograph when compared to the control women. Regarding POI, there was no association with UI, FI, and POP. NOS found that the quality assessment for these selected studies ranged from 5 to 8. We concluded that higher pelvic muscle activity and volume were found in women with PCOS, with further studies needed to confirm this data. Literature was scant about POI, CAH, and HPL.
Topics: Cross-Sectional Studies; Female; Humans; Pelvic Floor; Polycystic Ovary Syndrome; Prevalence; Urinary Incontinence
PubMed: 33331587
DOI: 10.1590/1806-9282.66.12.1742 -
Frontiers in Endocrinology 2020Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date... (Meta-Analysis)
Meta-Analysis
Decreased bone mineral density (BMD) is a concern in patients with congenital adrenal hyperplasia (CAH) due to lifelong glucocorticoid replacement. Studies till date have yielded conflicting results. We wanted to systematically evaluate the available evidence regarding BMD in adult patients with CAH. We searched Medline, Embase and Cochrane Central Register of Controlled Trials to identify eligible studies. Studies comparing BMD in CAH patients with age- and sex-matched controls were included. Age <16 years and absence of controls were exclusion criteria. Two authors independently reviewed abstracts, read full-text articles, extracted data, assessed risk of bias using Newcastle-Ottawa scale, and determined level of evidence using Grading of Recommendations Assessment, Development, and Evaluation methodology. Nine case-control studies with a total sample of 598 (cases = 254, controls = 344) met eligibility criteria. Median age was 31 years (IQR 23.9-37) and 65.7% were female. Total body BMD (Mean Difference [MD]-0.06; 95%CI -0.07, -0.04), lumbar spine BMD (MD -0.05; 95%CI -0.07, -0.03) and femoral neck BMD (MD -0.07; 95%CI -0.10, -0.05) was lower in cases compared to controls. Lumbar spine -scores (MD -0.86; 95%CI -1.16, -0.56) and -scores (MD -0.66; 95%CI -0.99, -0.32) and femoral neck -scores (MD -0.75 95%CI -0.95, -0.56) and -scores (MD -0.27 95%CI -0.58, 0.04) were lower in cases. BMD in adult patients with CAH was lower compared to controls. Although insufficient data precludes a dose-response relationship between glucocorticoid dose and BMD, it would be prudent to avoid overtreatment with glucocorticoids.
Topics: Adrenal Hyperplasia, Congenital; Bone Density; Bone and Bones; Case-Control Studies; Humans
PubMed: 32903805
DOI: 10.3389/fendo.2020.00493 -
Frontiers in Behavioral Neuroscience 2020Congenital adrenal hyperplasia (CAH) is a genetic condition of the steroidogenic enzymes in the adrenal cortex normally leading to variable degrees of cortisol and...
Congenital adrenal hyperplasia (CAH) is a genetic condition of the steroidogenic enzymes in the adrenal cortex normally leading to variable degrees of cortisol and aldosterone deficiency as well as androgen excess. Exposure to androgens prenatally might lead to ambiguous genitalia. The fetal brain develops in traditional male direction through a direct action of androgens on the developing nerve cells, or in the traditional female direction in the absence of androgens. This may indicate that sexual development, including sexual orientation, are programmed into our brain structures prenatally. The objective of this study was to perform a systematic review of the literature, investigating sexual orientation in individuals with CAH. The study also aimed at identifying which measures are used to define sexual orientation across studies. The review is based on articles identified through a comprehensive search of the OVIDMedline, PsycINFO, CINAHL, and Web of Science databases published up to May 2019. All peer-reviewed articles investigating sexual orientation in people with CAH were included. Quantitative, qualitative, and mixed methods were considered, as well as self-, parent-, and third-party reports, and no age or language restrictions were enforced on publications. The present review included 30 studies investigating sexual orientation in patients with CAH assigned female at birth (46, XX) ( = 927) or assigned male at birth (46, XY and 46, XX) ( = 274). Results indicate that assigned females at birth (46, XX) with CAH had a greater likelihood to not have an exclusively heterosexual orientation than females from the general population, whereas no assigned males at birth (46, XY or 46, XX) with CAH identified themselves as non-heterosexual. There was a wide diversity in measures used and a preference for unvalidated and self-constructed interviews. Hence, the results need to be interpreted with caution. Methodological weaknesses might have led to non-heterosexual orientation being overestimated or underestimated. The methodological challenges identified by this review should be further investigated in future studies.
PubMed: 32231525
DOI: 10.3389/fnbeh.2020.00038 -
The Cochrane Database of Systematic... Mar 2020Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition which leads to glucocorticoid deficiency and is the most common cause of adrenal insufficiency in children. In over 90% of cases, 21-hydroxylase enzyme deficiency is found which is caused by mutations in the 21-hydroxylase gene. Managing individuals with CAH due to 21-hydroxylase deficiency involves replacing glucocorticoids with oral glucocorticoids (including prednisolone and hydrocortisone), suppressing adrenocorticotrophic hormones and replacing mineralocorticoids to prevent salt wasting. During childhood, the main aims of treatment are to prevent adrenal crises and to achieve normal stature, optimal adult height and to undergo normal puberty. In adults, treatment aims to prevent adrenal crises, ensure normal fertility and to avoid the long-term consequences of glucocorticoid use. Current glucocorticoid treatment regimens can not optimally replicate the normal physiological cortisol level and over-treatment or under-treatment is often reported.
OBJECTIVES
To compare and determine the efficacy and safety of different glucocorticoid replacement regimens in the treatment of CAH due to 21-hydroxylase deficiency in children and adults.
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews, and trial registries (ClinicalTrials.gov and WHO ICTRP). Date of last search of trials register: 24 June 2019.
SELECTION CRITERIA
Randomised controlled trials (RCTs) or quasi-RCTs comparing different glucocorticoid replacement regimens for treating CAH due to 21-hydroxylase deficiency in children and adults.
DATA COLLECTION AND ANALYSIS
The authors independently extracted and analysed the data from different interventions. They undertook the comparisons separately and used GRADE to assess the quality of the evidence.
MAIN RESULTS
Searches identified 1729 records with 43 records subject to further examination. After screening, we included five RCTs (six references) with a total of 101 participants and identified a further six ongoing RCTs. The number of participants in each trial varied from six to 44, with participants' ages ranging from 3.6 months to 21 years. Four trials were of cross-over design and one was of parallel design. Duration of treatment ranged from two weeks to six months per treatment arm with an overall follow-up between six and 12 months for all trials. Overall, we judged the quality of the trials to be at moderate to high risk of bias; with lack of methodological detail leading to unclear or high risk of bias judgements across many of the domains. All trials employed an oral glucocorticoid replacement therapy, but with different daily schedules and dose levels. Three trials compared different dose schedules of hydrocortisone (HC), one three-arm trial compared HC to prednisolone (PD) and dexamethasone (DXA) and one trial compared HC with fludrocortisone to PD with fludrocortisone. Due to the heterogeneity of the trials and the limited amount of evidence, we were unable to perform any meta-analyses. No trials reported on quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility or final adult height. Five trials (101 participants) reported androgen normalisation but using different measurements (very low-quality evidence for all measurements). Five trials reported 17 hydroxyprogesterone (17 OHP) levels, four trials reported androstenedione, three trials reported testosterone and one trial reported dehydroepiandrosterone sulphate (DHEAS). After four weeks, results from one trial (15 participants) showed a high morning dose of HC or a high evening dose made little or no difference in 17 OHP, testosterone, androstenedione and DHEAS. One trial (27 participants) found that HC and DXA treatment suppressed 17 OHP and androstenedione more than PD treatment after six weeks and a further trial (eight participants) reported no difference in 17 OHP between the five different dosing schedules of HC at between four and six weeks. One trial (44 participants) comparing HC and PD found no differences in the values of 17 OHP, androstenedione and testosterone at one year. One trial (26 participants) of HC versus HC plus fludrocortisone found that at six months 17 OHP and androstenedione levels were more suppressed on HC alone, but there were no differences noted in testosterone levels. While no trials reported on absolute final adult height, we reported some surrogate markers. Three trials reported on growth and bone maturation and two trials reported on height velocity. One trial found height velocity was reduced at six months in 26 participants given once daily HC 25 mg/m²/day compared to once daily HC 15 mg/m²/day (both groups also received fludrocortisone 0.1 mg/day), but as the quality of the evidence was very low we are unsure whether the variation in HC dose caused the difference. There were no differences noted in growth hormone or IGF1 levels. The results from another trial (44 participants) indicate no difference in growth velocity between HC and PD at one year (very low-quality evidence), but this trial did report that once daily PD treatment may lead to better control of bone maturation compared to HC in prepubertal children and that the absolute change in bone age/chronological age ratio was higher in the HC group compared to the PD group.
AUTHORS' CONCLUSIONS
There are currently limited trials comparing the efficacy and safety of different glucocorticoid replacement regimens for treating 21-hydroxylase deficiency CAH in children and adults and we were unable to draw any firm conclusions based on the evidence that was presented in the included trials. No trials included long-term outcomes such as quality of life, prevention of adrenal crisis, presence of osteopenia, presence of testicular or ovarian adrenal rest tumours, subfertility and final adult height. There were no trials examining a modified-release formulation of HC or use of 24-hour circadian continuous subcutaneous infusion of hydrocortisone. As a consequence, uncertainty remains about the most effective form of glucocorticoid replacement therapy in CAH for children and adults. Future trials should include both children and adults with CAH. A longer duration of follow-up is required to monitor biochemical and clinical outcomes.
Topics: Adolescent; Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Dexamethasone; Glucocorticoids; Humans; Infant; Prednisolone; Quality of Life; Randomized Controlled Trials as Topic; Young Adult
PubMed: 32190901
DOI: 10.1002/14651858.CD012517.pub2 -
Frontiers in Endocrinology 2019Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000...
Twenty-one-hydroxylase-deficient non-classic adrenal hyperplasia (NC-CAH) is a very common autosomal recessive syndrome with prevalence between 1:1,000 and 1:2,000 individuals and the frequency varies according to ethnicity. On the other hand, polycystic ovary syndrome has a familial basis and it is inherited under a complex hereditary trait. This syndrome affects 6 to 10% of women in reproductive age and it is the most common endocrine disorder in young women. Our aim was to investigate, through a systematic review, the distinct characteristics and common findings of these syndromes. The search period covered January 1970 to November 2018, using the scientific databases PubMed. Inclusion criteria were adult women patients with PCOS or NC-CAH. Search terms were "polycystic ovary syndrome," "PCOS," "non-classical adrenal hyperplasia," "NC-CAH," "21-hydroxylase deficiency." From an initial 16,255 titles, the evaluations led to the final inclusion of 97 papers. The clinical features of NC-CAH are hirsutism and ovulatory and menstrual dysfunction therefore; differentiation between these two syndromes is difficult based on clinical grounds only. Additionally, NC-CAH and PCOS are both associated with obesity, insulin resistance, and dyslipidaemia. Reproductive abnormalities are also common between these hyperandrogenemic disorders since in patients with NC-CAH polycystic ovarian morphology and subfertility are present as they are in women with PCOS. The diagnosis of PCOS, is confirmed once other disorders that mimic PCOS have been excluded e.g., conditions that are related to oligoovulation or anovulation and/or hyperandrogenism, such as hyperprolactinaemia, thyroid disorders, non-classic congenital adrenal hyperplasia, and androgen-producing neoplasms. The screening tool to distinguish non-classic adrenal hyperplasia from PCOS is the measurement of 17-hydroxyprogesterone levels. The basal levels of 17-hydroxyprogesterone may overlap, but ACTH stimulation testing can distinguish the two entities. In this review these two common endocrine disorders are discussed in an effort to unveil their commonalities and to illuminate their shadowed distinctive characteristics.
PubMed: 31275245
DOI: 10.3389/fendo.2019.00388 -
Journal of the Endocrine Society Jun 2019Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that...
Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [ biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (17OHP) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower 17OHP and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.
PubMed: 31187081
DOI: 10.1210/js.2019-00136 -
Endocrine Oct 2018Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about...
PURPOSE
Congenital adrenal hyperplasia (CAH) has been shown to potentially affect psychological adjustment. However, most research has focused on females, and knowledge about psychological challenges in males remains sparse. The aim of this systematic review was therefore to assess these in males with CAH.
METHODS
We systematically searched the OVID Medline, PsycINFO, CINAHL, and Web of Science databases, for articles published up to April 20, 2018, investigating psychological adjustment in males with CAH.
RESULTS
Eleven studies were included in the review. Three main health domains were identified: psychological and psychiatric health, quality of life (QoL), and self-perceptions of reproductive health. Some studies covered more than one health domain. Seven studies explored psychological adjustment and/or the presence of psychiatric symptoms or disorders. Results indicated that males with CAH had more problems related to internalizing behaviors (negative behaviors directed toward the self) and more negative emotionality compared to reference groups. Six studies examined QoL, five of them reporting reduced QoL compared to reference groups. Three studies explored the impact of fertility and sexual health issues on psychological health with varying results from impaired to normal sexual well-being.
CONCLUSIONS
CAH seems to have an impact on males' psychological health. However, the number of identified studies was limited, included few participants, and revealed divergent findings, demonstrating the need for larger studies and highlighting a number of methodological challenges that should be addressed by future research.
Topics: Adrenal Hyperplasia, Congenital; Emotional Adjustment; Humans; Male; Mental Health; Quality of Life; Self Concept
PubMed: 30128958
DOI: 10.1007/s12020-018-1723-0